Amino aromatic esters for use as anaesthetics and method of making same



' Patented Nov. 20, 1928.

UNITED STATES 1,692,224 PATENT OFFICE.

IDUABD BITSEBT, Q1 IBAN KI'OBT-ON-THE-KLIN, GERMANY.

ammo anom'rrc nsrnnsroa can A8 ANEBTEETICS AND METHOD 0] MAKING sum.

7 No Drawing. Application filed April 27, 1998, Serial Io. 105,015, and in Germany Kay 14, 1885.

My invention refers to a new composition of matter adapted for use as an antise tie and local anaesthetic and to the metho of producing same.

As is well known to those skilled in the art the amino carboxylic esters, which are highly valued in their quality of non-poisonous local anaesthetics, are capable of formin with aromati'c sulfo acids salts, which in t eir dilute watery solutions do not exertv any corrosive action and are therefore also adapted to'serve for subcutaneous injections.

On the other hand these compounds are not suitable for treating open wounds inasmuch as their dilute solutions do not favor cicatrization and more concentrated solutions as well as the solid substances cause violent irritation or corrosion. The treatmentof open wounds has hitherto been carried out with mixtures of the pure amino benzoic acid ester with antiseptic'substances such as Dermatol or boric acid, in order to obtain inthis manner beside the sedative efiect also an antiseptic action. These mixtures, however, involve the great disadvantage that owing to the low melting point (below 100 C.) of the non-poisonous amino carboxylic acid esters they cannot be sterilized, so thatv their utilization for a good many purposes, for instance for the treatment of operated .surfaces, the injection in the form of powder suspensions and so on is rendered well nigh impossible.

According to the present invention I obtain compounds which are well ada ted for the treatment of wounds and which ve no corrosive action but simultaneously act as anaesthetics and antiseptics, b replacing the simle aromatic sulfo aci s by the aromatic alogenated sulfo acids such as the aromatic iodo sulfo acids or hromo sulfo acids or their derivatives or salts, which are made to react:

with the esters of the amino 'carboxylic acids or their derivatives or salts.

The halogenated sulfo acid salts of the amino carbo lic acid esters thus obtained are distinguis ed from the non-halogenated sulfo acid salts by dissolving in water only with great difiiculty. As compared with the carboxylic acid esters they involve the cat advantage of melting at a temperature a vs 1%? C. and therefore being easily steriliza e.

In consequence of their being diflicultly soluble the novel compounds, when being I of biiodo para phenol sulfo acid brought into contact with open wounds, produce an anaesthetic effect of long duration without exerting, any irritatin action. Their anaesthetic efiect isucombine with remarkable antiseptic roperties which are due notonly to their c emical components but" also'to their physical properties, more .espe cially to the great absorptive power.

The novel compounds are thus well adapted for the treatment of operation wounds,

burns and the like, but they can also be used urposes and more i vents being required. It is for instance possible to obtain reaction by causing the finely powdered components to act on each other in the presence 0 a small quantity of water or other suitable liquids, for instance blood serum. Y

Example 1.47.4 parts of the sodium salt BOIH poo-0:11:

urn-n01 in 500 parts of water. The novel compound tion of 21.5 parts resulting in the reaction and having the formula 0J1, OH I, SO;H NHp C H CQOC H; NaOl. s i

is precipitated almost quantitatively. It is separated from the liguid by filterin under pressure and is washe with water an if desired,also with alcohol. In order to obtain the product in its ure state for analysis it can be recrystallized sult white'needles which are easily soluble in alcohol, but more diflicultly in water and have .a melting oint of 225 C. (under decomposition); 1 hey have a fair anaesthetic action. Such arts of thenovel compound as have remain "over in'the mother liquor can be recovered by salting out.

Example 2.--A solution of 37.3-g. of the potassium salt of bibromo para phenol sulfo from alcohol. There re- I in ccms. water is made react with a solution of 20.5 g. ara amino benzoic acid ethyl ester hydroch oride NHa-HO] in 300 ccms. water and the product of reaction is subjected to further treatment as described with reference to Example 1. After recrystallization from alcohol the substance is obtained in the form of pure white crystals, melting at 193-200? C. and having a good anmsthetic action. Its formula is Ema/m Ze 8.-17.9 parts of para amino benzoic aci propyl ester.

oooolm' Example 4.-A solution of 47.4 'artsof the sodium salt of biiodo para .pheno sulfo acid in 500 parts of water is mixed with a soluara ammo benzoi'c acld propyl ester hydroc loride mixture is then allowed to cool filtered. When cooled down yellowish white.

own and is crystals separate out which are obtained by recrystallization from dilute alcohol withv ure white color and melting at 225-228 C. he product has the formula COOGIHY I in 500 parts of water and treated as described with reference to Example 1. There result white needles which are soluble in water with difliculty, but are easily solublein alcohol. They melt at 224 C. under decomposition and have a powerful anaesthetic action. The product has the formula Caron-ii-soar-NH,-o.H.-oooo.H,+Nao1.

I Example 5.A solution of 47.4 arts of the sodium salt of biiodo para pheno sulfo acid son:

in 500 parts of water is made to react with a solution of 22.95 parts of para amino benzoic acid isobutyl ester hydrochloride Example 6 .-47.4= parts of the sodium saltof loiiodo para phenol sulfo acid SOlH are intimatel triturated with 2015 parts of para amino enzoic acid ethyl ester hydrochloride and anaesthetic comprising combining an aromatic amino carboxylic acid ester witha compound containing a halogenated nonaliphatic sulfo acid radical.

2. The method of producing an antiseptic and anaesthetic comprising combining an aromatic amino carboxylic acid ester with a compound containing a halogenated aromatic sulfo acid radical.

3. The method of producing an antiseptic and anaesthetic comprising combining an OOOOQHI m-noi in 100 parts of water the further treatment being carried out as described with reference .to Example 1. There result white needles having a silky gloss, which dissolve easily in alcohol, with difficulty in water, which melt under decomposition at 222-224 C. and have a powerful anaesthetic action. The product has the formula C H; N301.

COO-02H:

and are mixed with 150 parts of water. The mixture which at first is thinly fluid, solidifies with the reaction to a brittle mass which after having been subjected to pressure can be dried at low temperature or can be treated further as described with reference to Example 1. There result the same substances as those obtained from the. solution, viz, white needles melting at 223225 and having a powerful anaesthetic action. The product has the formula aromatioamino carboxylic acid ester with a compound containing a non-aliphatic iodo sulfo radical.

4. The method of producing an antiseptic and anaesthetic comprising combining an aromatic amino carboxylic acid ester with a compound contam'mg an aromatic iodo sulfo acld radical.

Ill! 5. As a new composition of matter, a halogenated non-aliphatic sulfo acid com-v pound of an amido carboxylic acid ester, being soluble in water only with great difficulty, having a melting point above C. and a powerful antiseptic and anaesthetic effect.

6. As a new composition of matter, a nonaliphatic iodo sulfo acid compound of an amido carboxy'lic acidester, being soluble in water only with great difiiculty,-having a melting point above 100 'C. and a powerful antiseptic and anaesthetic effect.

In testimony whereof I afiix my signature.

EDUARD RITSERT. 

